Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced positive data from the Phase I/II STARTRK-NG study, evaluating the investigational medicine entrectinib in children and adolescents with recurrent or refractory solid tumors with and without neurotrophic tyrosine receptor kinase (NTRK), ROS1 or anaplastic lymphoma kinase (ALK) gene fusions. The study showed entrectinib shrank tumors (objective response rate; ORR) in all children and adolescents who had NTRK, ROS1 or ALK fusion-positive solid tumors (11 of 11 patients), including two patients achieving a complete response. Of the 11 patients, five patients with primary high-grade tumors in the central nervous system (CNS) had an objective response, including one patient with a complete response. The safety profile of entrectinib was consistent with that seen in previous analyses. Data will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on Sunday, June 2, 2019, from 8:00 – 8:12 a.m. CDT (Abstract 10009), and was part of today’s official ASCO presscast.

“We are encouraged by the results we have seen with entrectinib in children with pediatric and adolescent cancers, including those with tumors in the brain,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “The STARTRK-NG study underscores the importance of combining comprehensive genomic profiling with targeted therapies and supports our approach to providing people with personalized medicines developed specifically for their type of cancer.”

Additional data for entrectinib across different tumor types and patient populations will also be presented at ASCO, highlighting the company’s unique approach to personalized healthcare through advances in targeted therapies, diagnostics and data analytics:

Initial results from an integrated analysis of the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials evaluating the efficacy of entrectinib in adults with solid tumors and CNS metastases will be presented on Saturday, June 1, 2019, in a poster session from 3:00 – 4:30 p.m. CDT (Abstract 3017).

Results from a real-world data study evaluating time-to-treatment discontinuation and progression-free survival as endpoints for comparative efficacy analysis of clinical trials of entrectinib and crizotinib for the treatment of people with ROS1-positive non-small cell lung cancer (NSCLC) will be presented during a poster session on Sunday, June 2, 2019, from 8:00 – 11:00 a.m. CDT (Abstract 9070).

The FDA recently granted Priority Review for entrectinib for both the treatment of pediatric and adult patients with NTRK fusion-positive, locally advanced or metastatic solid tumors who have either progressed following prior therapies or as an initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic ROS1-positive NSCLC. These NDAs are based on results from the integrated analysis of the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and data from the STARTRK-NG study. The FDA is expected to make a decision on approval by August 18, 2019.

About the STARTRK-NG study

STARTRK-NG is a Phase I/II open-label dose-escalation and expansion study evaluating the safety and efficacy of entrectinib in children and adolescent patients with no curative first-line treatment option, recurrent or refractory extracranial solid tumors or primary CNS tumors, with or without NTRK, ROS1 or ALK fusions. Response, assessed by Investigator, was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) using Response Assessment in Neuro-Oncology (RANO) for CNS tumors, Response Evaluation Criteria in Solid Tumors (RECIST), and Curie score (CS) for neuroblastoma. The study enrolled 29 children and adolescents aged 4.9 months through 20 years (median age of 7 years) who had recurrent or refractory solid tumors, and 28 were evaluated for response. Of the 28 children and adolescents evaluated, 11 children were identified to have tumors with NTRK, ROS1 or ALK fusions and one with ALK F1174L-mutated neuroblastoma. A summary of the results are included below.

Complete responses were observed in two patients with tumors harboring NTRK and ALK fusions: one with an NTRK fusion-positive primary CNS tumor and one with an ALK fusion-positive inflammatory myofibroblastic tumor. Another complete response was observed in one neuroblastoma patient with an ALK F1174L mutation.

Partial responses were observed in nine patients, three unconfirmed at the time of the clinical cut-off date, across NTRK, ROS1 and ALK fusion-positive primary CNS (n=4) and extracranial (n=5) solid tumors.

Median duration of therapy for confirmed fusion-positive responders was 10.51 months (3.8 to 17.7 months), and median time to response was 1.89 months (1 to 1.9 months).

The safety profile of entrectinib was consistent with that seen in previous analyses. Treatment-related adverse events were most frequently National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or 2, leading to discontinuation in 6.9 percent of patients.

About NTRK fusion-positive cancer

Neurotrophic tyrosine receptor kinase (NTRK) fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling pathways involved in proliferation of certain types of cancer. NTRK gene fusions are tumor-agnostic, meaning they are present in tumors irrespective of site of origin. These fusions have been identified in a broad range of solid tumor types, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

About entrectinib

Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumors that harbor NTRK1/2/3 or ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions. Entrectinib is being investigated across a range of solid tumor types, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.